• Keine Ergebnisse gefunden

1. Cleland, J.G., A. Khand, and A. Clark, The heart failure epidemic: exactly how big is it?

Eur Heart J, 2001. 22(8): p. 623-6.

2. Kannel, W.B. and A.J. Belanger, Epidemiology of heart failure. Am Heart J, 1991. 121(3 Pt 1): p. 951-7.

3. Ho, K.K., et al., Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation, 1993. 88(1): p. 107-15.

4. Cowie, M.R., et al., The epidemiology of heart failure. Eur Heart J, 1997. 18(2): p. 208-25.

5. Levy, D., et al., The progression from hypertension to congestive heart failure. Jama, 1996. 275(20): p. 1557-62.

6. Liao, Y., et al., Left ventricular hypertrophy has a greater impact on survival in women than in men. Circulation, 1995. 92(4): p. 805-10.

7. Remme, W.J. and K. Swedberg, Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J, 2001. 22(17): p. 1527-60.

8. Braunwald, E., et al., Braunwald's Heart Disease, 5th Edition, 1997. 1(13): p. 394-415.

9. Cleland, J.G., et al., The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J, 2003. 24(5): p. 442-63.

10. Owan, T.E., et al., Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med, 2006. 355(3): p. 251-9.

11. Regitz-Zagrosek, V., S. Brokat, and C. Tschope, Role of gender in heart failure with normal left ventricular ejection fraction. Prog Cardiovasc Dis, 2007. 49(4): p. 241-51.

12. Brutsaert, D.L., Cardiac dysfunction in heart failure: the cardiologist's love affair with time. Prog Cardiovasc Dis, 2006. 49(3): p. 157-81.

13. De Keulenaer, G.W. and D.L. Brutsaert, Diastolic heart failure: a separate disease or selection bias? Prog Cardiovasc Dis, 2007. 49(4): p. 275-83.

14. Masoudi, F.A., et al., Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol, 2003. 41(2): p. 217-23.

15. Devereux, R.B., et al., Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the Strong Heart Study. Am J Cardiol, 2000.

86(10): p. 1090-6.

16. Redfield, M.M., et al., Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. Jama, 2003. 289(2): p.

194-202.

17. Fischer, M., et al., Prevalence of left ventricular diastolic dysfunction in the community.

Results from a Doppler echocardiographic-based survey of a population sample. Eur Heart J, 2003. 24(4): p. 320-8.

18. Hayward, C.S., W.V. Kalnins, and R.P. Kelly, Gender-related differences in left ventricular chamber function. Cardiovasc Res, 2001. 49(2): p. 340-50.

19. O'Meara, E., et al., Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure:

Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation, 2007. 115(24): p. 3111-20.

20. Krumholz, H.M., M. Larson, and D. Levy, Sex differences in cardiac adaptation to isolated systolic hypertension. Am J Cardiol, 1993. 72(3): p. 310-3.

21. Kuch, B., et al., Gender specific differences in left ventricular adaptation to obesity and hypertension. J Hum Hypertens, 1998. 12(10): p. 685-91.

22. Kuch, B., et al., Body composition and prevalence of left ventricular hypertrophy.

Circulation, 2000. 102(4): p. 405-10.

23. Kawaguchi, M., et al., Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation, 2003. 107(5): p. 714-20.

24. Klein, A.L., et al., Effects of age on left ventricular dimensions and filling dynamics in 117 normal persons. Mayo Clin Proc, 1994. 69(3): p. 212-24.

25. Lakatta, E.G. and D. Levy, Arterial and cardiac aging: major shareholders in

cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease.

Circulation, 2003. 107(1): p. 139-46.

26. Lakatta, E.G., Cardiovascular regulatory mechanisms in advanced age. Physiol Rev, 1993. 73(2): p. 413-67.

27. Redfield, M.M., et al., Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation, 2005. 112(15): p. 2254-62.

28. Lakatta, E.G. and D. Levy, Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation, 2003. 107(2): p. 346-54.

29. Yamakado, T., et al., Effects of aging on left ventricular relaxation in humans. Analysis of left ventricular isovolumic pressure decay. Circulation, 1997. 95(4): p. 917-23.

30. Chen, C.H., et al., Coupled systolic-ventricular and vascular stiffening with age:

32. Smulyan, H., et al., Comparative effects of aging in men and women on the properties of the arterial tree. J Am Coll Cardiol, 2001. 37(5): p. 1374-80.

33. Hundley, W.G., et al., Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol, 2001. 38(3): p. 796-802.

34. Wong, C.Y., et al., Alterations of left ventricular myocardial characteristics associated with obesity. Circulation, 2004. 110(19): p. 3081-7.

35. Karamitsos, T.D., et al., Early diastolic impairment of diabetic heart: the significance of right ventricle. Int J Cardiol, 2007. 114(2): p. 218-23.

36. Kannel, W.B., M. Hjortland, and W.P. Castelli, Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol, 1974. 34(1): p. 29-34.

37. Regitz-Zagrosek, V., Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nat Rev Drug Discov, 2006. 5(5): p. 425-38.

38. Regitz-Zagrosek, V. and E. Lehmkuhl, Heart failure and its treatment in women. Role of hypertension, diabetes, and estrogen. Herz, 2005. 30(5): p. 356-67.

39. Regitz-Zagrosek, V., et al., Gender aspects in heart failure. Pathophysiology and medical therapy. Arch Mal Coeur Vaiss, 2004. 97(9): p. 899-908.

40. Regitz-Zagrosek, V., E. Lehmkuhl, and M.O. Weickert, Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol, 2006.

95(3): p. 136-47.

41. Carroll, J.D., et al., Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation, 1992. 86(4): p. 1099-107.

42. Aurigemma, G.P., et al., Impact of chamber geometry and gender on left ventricular systolic function in patients > 60 years of age with aortic stenosis. Am J Cardiol, 1994.

74(8): p. 794-8.

43. Douglas, P.S., et al., Gender differences in left ventricle geometry and function in patients undergoing balloon dilatation of the aortic valve for isolated aortic stenosis.

NHLBI Balloon Valvuloplasty Registry. Br Heart J, 1995. 73(6): p. 548-54.

44. Villari, B., et al., Sex-dependent differences in left ventricular function and structure in chronic pressure overload. Eur Heart J, 1995. 16(10): p. 1410-9.

45. Legget, M.E., et al., Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis. Am Heart J, 1996. 131(1): p. 94-100.

46. Krayenbuehl, H.P., et al., Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement. Circulation, 1989. 79(4): p.

744-55.

47. Monrad, E.S., et al., Time course of regression of left ventricular hypertrophy after aortic valve replacement. Circulation, 1988. 77(6): p. 1345-55.

48. Douglas, P.S., et al., Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload. J Am Coll Cardiol, 1998. 32(4): p. 1118-25.

49. Tamura, T., S. Said, and A.M. Gerdes, Gender-related differences in myocyte remodeling in progression to heart failure. Hypertension, 1999. 33(2): p. 676-80.

50. Fielitz, J., et al., Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis. J Mol Med, 2004. 82(12): p. 809-20.

51. Fielitz, J., et al., Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. J Am Coll Cardiol, 2001.

37(5): p. 1443-9.

52. Fielitz, J., et al., Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure. Circulation, 2002. 105(3): p. 286-9.

53. Nordmeyer, J., et al., Upregulation of myocardial estrogen receptors in human aortic stenosis. Circulation, 2004. 110(20): p. 3270-5.

54. Thiele, B.J., et al., RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are involved in post-transcriptional control of collagen I and III synthesis. Circ Res, 2004. 95(11): p. 1058-66.

55. Mahmoodzadeh, S., et al., Estrogen receptor alpha up-regulation and redistribution in human heart failure. Faseb J, 2006. 20(7): p. 926-34.

56. Frey, N., et al., Hypertrophy of the heart: a new therapeutic target? Circulation, 2004.

109(13): p. 1580-9.

57. Weinberg, E.O., et al., Sex dependence and temporal dependence of the left ventricular genomic response to pressure overload. Physiol Genomics, 2003. 12(2): p. 113-27.

58. Witt, H., et al., Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med, 2008. 86(9): p. 1013-24.

59. Kong, S.W., et al., Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats. Physiol Genomics, 2005. 21(1): p. 34-42.

60. Codd, E.F., A relational model of data for large shared data banks. Commun. ACM, 1970. 13(6): p. 377-387.

61. Lang, R.M., et al., Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr, 2005. 18(12): p. 1440-63.

62. Gottdiener, J.S., et al., American Society of Echocardiography recommendations for use of echocardiography in clinical trials. J Am Soc Echocardiogr, 2004. 17(10): p. 1086-119.

63. Devereux, R.B., et al., Echocardiographic assessment of left ventricular hypertrophy:

comparison to necropsy findings. Am J Cardiol, 1986. 57(6): p. 450-8.

65. de Simone, G., et al., Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol, 1992. 20(5): p. 1251-60.

66. de Simone, G., et al., Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults. Hypertension, 1994. 23(5): p. 600-6.

67. Wilson, E.M., et al., Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation, 2003. 107(22): p. 2857-63.

68. Pelliccia, A., et al., Physiologic left ventricular cavity dilatation in elite athletes. Ann Intern Med, 1999. 130(1): p. 23-31.

69. Dewey, F.E., et al., Does size matter? Clinical applications of scaling cardiac size and function for body size. Circulation, 2008. 117(17): p. 2279-87.

70. Schmidt-Nielsen, K., Scaling: Why is Animal Size So Important? New York, NY:Cambridge University Press, 1984.

71. Villa, E., et al., Factors affecting left ventricular remodeling after valve replacement for aortic stenosis. An overview. Cardiovasc Ultrasound, 2006. 4: p. 25.

72. Forman, D.E., et al., Cardiac morphology and function in senescent rats: gender-related differences. J Am Coll Cardiol, 1997. 30(7): p. 1872-7.

73. Klein, L.E., et al., Upregulation of collagen type I gene expression in the ventricular myocardium of thyroidectomized male and female rats. J Mol Cell Cardiol, 1996. 28(1):

p. 33-42.

74. Davis, D.R., et al., The development of cardiac fibrosis in low tissue factor mice is gender-dependent and is associated with differential regulation of urokinase plasminogen activator. J Mol Cell Cardiol, 2007. 42(3): p. 559-71.

75. Tasca, G., et al., Impact of valve prosthesis-patient mismatch on left ventricular mass regression following aortic valve replacement. Ann Thorac Surg, 2005. 79(2): p. 505-10.

76. Del Rizzo, D.F., et al., Factors affecting left ventricular mass regression after aortic valve replacement with stentless valves. Semin Thorac Cardiovasc Surg, 1999. 11(4 Suppl 1):

p. 114-20.

77. Gelsomino, S., et al., Time course of left ventricular remodeling after stentless aortic valve replacement. Am Heart J, 2001. 142(3): p. 556-62.

78. Kuhl, H.P., et al., Regression of left ventricular mass one year after aortic valve replacement for pure severe aortic stenosis. Am J Cardiol, 2002. 89(4): p. 408-13.

79. Braunwald, E., et al., Braunwald's Heart Disease, 5th Edition, 1997. 2(61): p. 1902-1905.

80. Westermann, D., et al., Tumor necrosis factor-alpha antagonism protects from myocardial inflammation and fibrosis in experimental diabetic cardiomyopathy. Basic Res Cardiol, 2007. 102(6): p. 500-7.

81. Rodondi, N., et al., Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study. J Am Coll Cardiol, 2008. 52(14): p. 1152-9.

82. Fommei, E. and G. Iervasi, The role of thyroid hormone in blood pressure homeostasis:

evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab, 2002.

87(5): p. 1996-2000.

83. Moran, A., et al., Left ventricular hypertrophy in mild and moderate reduction in kidney function determined using cardiac magnetic resonance imaging and cystatin C: the multi-ethnic study of atherosclerosis (MESA). Am J Kidney Dis, 2008. 52(5): p. 839-48.

84. Rady, M.Y., T. Ryan, and N.J. Starr, Perioperative determinants of morbidity and mortality in elderly patients undergoing cardiac surgery. Crit Care Med, 1998. 26(2): p.

225-35.

8. Tabellenverzeichnis

Tabelle 1: Formeln zur Berechnung der BSA und Alter entsprechenden Normwerte ... 19

Tabelle 2: Klinische Charakteristika der molekularbiologisch untersuchten Patienten ... 21

Tabelle 3: RNA-Konzentrationsmessung: Übersicht über die eingesetzten Reagenzien... 22

Tabelle 4: Demographische und anthropometrische Angaben zur Studienpopulation ... 35

Tabelle 5: Klinischer Status der Patienten bei Aufnahme in die Studie ... 37

Tabelle 6: Rhythmusanalyse ... 38

Tabelle 7: Nierenfunktion ... 38

Tabelle 8: Medikation bei Aufnahme... 39

Tabelle 9: Intraoperativer Verlauf und Komplikationen... 41

Tabelle 10: Frühpostoperative Komplikationen und Mortalität ... 42

Tabelle 11: Morphologie von Aorten- und Mitralklappe in der präop. Echokardiographie .... 43

Tabelle 12: Präoperativ ausgewählte echokardiographische Parameter ... 44

Tabelle 13: Verteilung präoperativ gemessener Echoparameter als Norm- und path. vergrößerte Werte ... 46

Tabelle 14: Postoperativ ausgewählte echokardiographische Parameter ... 46

Tabelle 15: Verteilung frühpostoperativ gemessener Echoparameter als Norm- und path. vergrößerte Werte ... 48

Tabelle 16: Hypertrophieprävalenz bei Patienten mit AS vor und nach AKE... 49

9. Abbildungsverzeichnis

Abbildung 1: Vorbereitung und Beladen der Chips mit den Reagenzien und RNA-Proben . 23

Abbildung 2: RNA-Qualitätskontrolle mit Hilfe des Bioanalyzers ... 23

Abbildung 3: RNA-Qualitätskontrolle: Übersicht der Chipauswertung ... 24

Abbildung 4: RNA-Qualitätskontrolle: Gelähnliche Darstellung der Chipauswertung ... 25

Abbildung 5: RNA Quantifizierung: Punktdiagramme zur Darstellung der Ausreißer ... 27

Abbildung 6: Schematische Übersicht der Datenbankstruktur ... 29

Abbildung 7: Patientenregistration im Formular „Patientenstammdaten“ ... 30

Abbildung 8: Eingabe der Untersuchungsdaten im Formular „Untersuchungen“... 31

Abbildung 9: Schema der zeitlichen Validierung der Daten in der 4H-Datenbank ... 34

Abbildung 10: LV-Diameter in der präoperativen Echokardiographie ... 44

Abbildung 11: Verteilung der beobachteten Werte in Norm- und pathologischen Werten ... 45

Abbildung 12: LV-Diameter in der postoperativen Echokardiographie ... 47

Abbildung 13: Geschlechtsspezifische Trends in der LV-Geometrie vor und nach AKE ... 51

Abbildung 14: GU in der Expression von Collagen und MMP bei Patienten mit AS ... 52 Abbildung 15: Korrelation von MMP-9 mRNA Expression mit LVEDD bei Patienten mit AS . 53

Danksagung

Mein besonderer und ausgesprochen herzlicher Dank gilt meiner Doktormutter Fr. Prof. Regitz-Zagrosek für eine sehr gute und umfassende Betreuung. Ich danke insbesondere für die fachliche Motivation, für die konstruktive Kritik bei der Aufarbeitung der Ergebnisse und ganz besonders für die hohe Anerkennung, die ein wesentlicher Motor war.

Dem Operationsteam im DHZB und insbesondere Herrn Prof. Hetzer danke Ich herzlich für die Unterstützung im Operationssaal. Prof. Hetzer hat die Studie jederzeit unterstützt und den größten Anteil der Septumresektionen durchgeführt und somit maßgeblich zum Erfolg der Studie beigetragen.

Frau Dr. Lehmkuhl, Frau Dr. Jurmann und Fr. Dr. Schubert danke ich für eine herausragende Betreuung im DHZB und CCR. Ich bedanke mich insgesamt für die Möglichkeit der Zusammen-arbeit mit dem Institut für Geschlechter in der Medizin und die freundliche Aufnahme dort.

Lebenslauf

Mein Lebenslauf wird aus datenschutzrechtlichen Gründen in der elektronischen Version meiner Arbeit nicht veröffentlicht.